Age is an independent risk factor for NIDDM. Age is also associated with a decline in insulin secretion. Using 6-cells from Wistar rats from the colony of aged rats at the GRC, we showed that insulin release in response to glucose decreases with age of the donor. This is a result of fewer beta cells releasing insulin as well as less insulin released per cell. We found that mRNA for insulin is preferentially diminished in islets, with glucokinase and glucagon messages unaffected. Therefore, it appears that throughout the lifespan of the rat, insulin message is decreasing. Islets compensate for this by increasing size. But, eventually this compensation becomes inadequate. Therefore, one can envision when a stress is put on the system so more insulin is required, diabetes could result. We are exploring what factors lead to this diminution of insulin message and the possibility that we can prevent or reverse it.